PROJECT SUMMARY Lower limb amputees often complain about uncomfortable skin temperatures and the accumulation of perspiration within their prostheses. Activities, such as walking, cause substantial increases in skin temperatures such that additional bouts of activity, even when interspersed with rest periods longer than the activity periods, result in a cumulative increase in skin temperature through the course of a typical day. One reason is that the materials from which their prostheses are constructed are extremely effective insulators and impermeable to moisture; trapping heat and accumulating sweat inside the prosthesis. Amputee thermoregulation may be further complicated by neuronal degradation impairing temperature sensation and vasomotor response. To address this important Veteran amputee issue, we have already built a novel instrument to simultaneously measure skin temperature perception thresholds and thermoregulatory responses to changing skin temperature conditions. We have also built a unique thermal manikin with which we can optimize the design of a prototype prosthesis intended to provide thermal relief and expel accumulated sweat. Our proposed research will use this instrument and thermal manikin to accomplish three specific aims. Specific Aim 1 will identify perception thresholds to thermal stimuli and the existence of any amputation- or diabetic-related thermoregulatory impairment. We will use a novel instrument to study the effect of changing skin temperature on healthy non-amputees (n=20), lower limb amputees of traumatic etiology (n=20), and lower limb amputees of diabetic etiology (n=20). This instrument will enable us to measure the skin temperatures at which participants can perceive warm and cold stimuli. At the same time, we will also measure changes in local blood flow; an important thermoregulatory strategy. Data from this experiment will enable hypothesis testing to distinguish population-specific differences. Specific Aim 2 will use a unique thermal manikin to optimize the design of a novel, dynamic air exchange prosthesis intended to provide thermal relief and expel accumulated sweat. We have already built a prototype of this prosthesis and observed promising results in our preliminary human subject experiments. To facilitate design improvements we built a thermal manikin to physically simulate the residual lower limb. We plan to use this experimental model in bench-top experiments to optimize the location and number of inflow ports, pressure differentials, and the controller operation of our novel prosthesis. Specifi Aim 3 will determine if our optimized, dynamic air exchange prosthesis can maintain lower, more comfortable skin temperatures and reduce sweating than the current standard of care, a prosthesis with a distal locking pin suspension. We will conduct a within-subject comparison test involving the participation of traumatic (n=10) and diabetic (n=10) lower limb amputees. Data from this experiment will enable hypothesis testing to directly compare the two prostheses in terms of skin temperature, sweat, and thermal comfort. The proposed research will provide a thorough understanding of thermal perception and physiologic response in the amputee population and provide for a direct comparison between a novel prosthesis intended to provide thermal relief and a prosthesis prescribed to many lower limb amputees. The evidence-based understanding and prosthetic technology innovations resulting from the proposed research are expected to measurably improve the life experiences of lower limb amputees. PUBLIC HEALTH RELEVANCE: RELEVANCE OF THE PROPOSED RESEARCH TO VETERANS Between 3000 and 5000 lower limb amputation surgeries are performed each year on Veterans (Mayfield et al., 2000). These Veterans are among the 623,000 Americans who live with lower limb amputation, a population expected to grow as our nation's population ages (Ziegler-Graham et al., 2008). Further, U.S. involvements in military conflicts overseas are resulting in additional amputees of traumatic etiology; a population who will rely on the VA for years to come. Developing innovative approaches to improve their rehabilitative care is a VA priority. The proposed research will yield key knowledge needed to develop and commercialize the next generation of prostheses that can maintain comfortable temperatures and ameliorate the adverse effects of sweating by the residual limb. We believe that the knowledge disseminated from this research will lead to substantial improvements in the quality of life of Veteran amputees.